Triethylamine → 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

HRID 1453358Notes

Reaction equation

HRID 1453358 reaction equation
[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([O:21]C)=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.C[C@H]1NCCN(C(=O)C2C=CC=CC=2)C1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68832135methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylateHCID 68840483HCID 68840483, compound

Product 1

HCID 666396797H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (200 mg, 0.48 mmol), 3(R)-methyl-1-benzoylpiperazine hydrochloride (130 mg, 0.58 mmol) and triethylamine (0.20 mL) in DMF (3 mL) was added HATU (220 mg, 0.58 mmol). The reaction mixture was stirred at rt for 1 h, diluted with H2O (˜5 mL) stirred for 30 min, and the solids (290 mg) collected by filtration and flushed with H2O. The crude solids were dissolved into MeOH/THF (1:1, 4 mL) and treated with 1M aqueous NaOH (0.75 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 15 min in a sealed tube. The clear solution was diluted with H2O (5 mL), neutralized with 1M aqueous HCl (0.75 mL) and concentrated to remove organic solvents. The resultant solids were collected by filtration, washed with H2O and dried under vacuum to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 6-[[(2R)-4-benzoyl-2-methyl-1-piperazinyl]carbonyl]-13-cyclohexyl (257 mg, 0.44 mol, 90%). LCMS: m/e 586 (M−H)−, ret time 1.48 min, column A, 2 minute gradient.

Workup

  1. stirringstirred for 30 min
  2. filtrationthe solids (290 mg) collected by filtration
  3. customflushed with H2O
  4. dissolutionThe crude solids were dissolved into MeOH/THF (1:1, 4 mL)
  5. additiontreated with 1M aqueous NaOH (0.75 mL)
  6. stirringThe reaction mixture was stirred
  7. temperatureheated at 80° C. with microwave irradiation for 15 min in a sealed tube
  8. additionThe clear solution was diluted with H2O (5 mL)
  9. concentrationconcentrated
  10. customto remove organic solvents
  11. filtrationThe resultant solids were collected by filtration
  12. washwashed with H2O
  13. customdried under vacuum

Sources & evidence

ORD record
ord-83ae40df47494e71ae3ae2c463e84167
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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